Long acting cabotegravir: updated efficacy and safety results from HPTN 084


BACKGROUND: HPTN 084 is an ongoing Phase 3 randomized, controlled trial that demonstrated the superiority of long-acting injectable cabotegravir (CAB) compared to daily oral TDF/FTC for HIV prevention in individuals assigned female at birth. The blinded portion of the trial was stopped at a planned interim review in November 2020. Participants were subsequently unblinded and continued on their original randomised study regimen pending a protocol amendment to offer open-label CAB.

METHODS: We report on HIV infections detected in the 12-month period following trial unblinding (11/5/20-11/5/21, detected through 12/31/21) based on site and HPTN Laboratory Center testing. We estimated cumulative HIV incidence for the combined primary blinded and 12-month unblinded follow-up period, by study arm. Grade 2+ adverse events (AEs), injection site reactions (ISR), pregnancy incidence and outcomes are reported for the 12-month post-unblinding period only.
RESULTS: Twenty-three incident infections (3 CAB, 20 TDF/FTC) were detected in the 12-month unblinded period. Of these, two (1 CAB, 1 TDF/FTC) were determined to have occurred during the blinded phase. Only one of the CAB cases (blinded phase case) had ever received an injection. Cumulatively, 62 incident HIV infections (6 CAB, 56 TDF/FTC) have been observed over 6626 person-years of follow up (HIV incidence 0.94%, 95% CI 0.72, 1.20). The superiority of CAB appears sustained (HR 0.11, 95% CI 0.05, 0.24). No new safety concerns were identified. For the 12-month unblinded period, 2.4% (32/1318) of participants in the CAB group reported a Grade 2+ ISR. Overall, Grade 2+ AEs in this period were balanced by study group; 20% were assessed as related to study product (CAB 19%, TDF/FTC 21%). Two deaths occurred in the CAB group; both were assessed as unrelated to study product. An additional 83 confirmed pregnancies (43 CAB, 40 TDF/FTC) occurred in the unblinded period (incidence 3.20%, 95% CI 2.56, 3.98). No congenital anomalies were reported.
CONCLUSIONS: Reductions in HIV incidence were sustained. CAB continues to be superior to TDF/FTC in preventing HIV infection in individuals assigned female at birth. Pregnancy incidence was higher in the unblinded period highlighting the importance of ongoing evaluations of CAB safety in pregnancy.